Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala
Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala
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DOI：
10.1073/pnas.0802302105
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发表时间：
2008-06-17
影响因子：
11.1
通讯作者：
Roberto, Marisa
中科院分区：
文献类型：
--
作者：
Bajo, Michal;Cruz, Maureen T.;Roberto, Marisa
在中央杏仁核（CeA）中，乙醇通过促肾上腺皮质激素释放因子（CRF）1型受体发挥作用，以增强γ-氨基丁酸（GABA）的释放。杏仁核的CRF介导与应激和药物依赖相关的焦虑，并调节乙醇摄入。由于缺乏蛋白激酶C ε（PKC ε）的突变小鼠表现出焦虑样行为减少和酒精消耗量降低，我们研究了PKC ε是否位于CeA中CRF1受体的下游。与PKC ε（+/+）CeA神经元相比，PKC ε（-/-）神经元由于GABA释放增强而显示出γ-氨基丁酸能张力增加。CRF和乙醇刺激PKC ε（+/+）CeA中的GABA释放，但不刺激PKC ε（-/-）CeA中的GABA释放。一种PKC ε特异性抑制剂阻断了PKC ε（+/+）CeA中CRF和乙醇诱导的GABA释放，这证实了在PKC ε（-/-）CeA中的发现。这些结果确定了CeA中的一个PKC ε信号通路，该通路被CRF1受体刺激激活，介导神经末梢的GABA释放，并调节焦虑和酒精消耗。
In the central amygdala (CeA), ethanol acts via corticotrophin-releasing factor (CRF) type 1 receptors to enhance GABA release. Amygdala CRF mediates anxiety associated with stress and drug dependence, and it regulates ethanol intake. Because mutant mice that lack PKC epsilon exhibit reduced anxiety-like behavior and alcohol consumption, we investigated whether PKC epsilon lies downstream of CRF1 receptors in the CeA. Compared with PKC epsilon(+/+) CeA neurons, PKC epsilon(-/-) neurons showed increased GABAergic tone due to enhanced GABA release. CRF and ethanol stimulated GABA release in the PKC epsilon(+/+) CeA, but not in the PKC epsilon(-/-) CeA. A PKCE-specific inhibitor blocked both CRF- and ethanol-induced GABA release in the PKC epsilon(+/+) CeA, confirming findings in the PKC epsilon(-/-) CeA. These results identify a PKCE signaling pathway in the CeA that is activated by CRF1 receptor stimulation, mediates GABA release at nerve terminals, and regulates anxiety and alcohol consumption.